Common Painkillers May Blunt Antidepressants.
Common over-the-counter painkillers such as ibuprofen, aspirin and naproxen may reduce the effectiveness of antidepressants called selective serotonin reuptake inhibitors, or SSRIs, according to a mouse and human study from The Rockefeller University in New York City.

SSRIs -- which are the most common antidepressants and are used by millions of people. The potential interaction between these drugs and the painkillers known as nonsteroidal anti-inflammatory drugs (NSAIDs) may be a reason that some people don't respond to SSRIs, the researchers report.

"In one study, we found that anyone who reported use of an anti-inflammatory or analgesic agent had a much poorer treatment outcome compared to people who didn't report any use of NSAIDs," said study lead author Jennifer Warner-Schmidt.

One of the open questions is what dose is needed over what time period to produce this effect, said Warner-Schmidt, a research associate in the university's laboratory of molecular and cellular neuroscience. "Until a double-blind real clinical trial is done, we can't say what the dose is [or] what the time course is," she said.

"We may only be looking at people who are taking NSAIDs over a long period of time, but it's not clear," she explained.

In addition, why NSAIDs blunt the effect of SSRIs isn't known, Warner-Schmidt said, adding that "we have some speculative hypotheses we will be exploring in further studies."
Even with these caveats, Warner-Schmidt characterizes the effect of the interaction between these drugs as strong.

"If people out there are having trouble with SSRI efficacy and they happen to be taking anti-inflammatory drugs, they may want to speak with their clinician to evaluate whether they need to continue on the anti-inflammatory drugs, and if so, they may consider changing their antidepressant to a different class of antidepressant," Warner-Schmidt said.

For their study, the researchers gave mice SSRIs with and without NSAIDs. By looking at how the mice behaved in tasks sensitive to antidepressants, the researchers found those behaviors inhibited in the mice given NSAIDs.

Warner-Schmidt's team confirmed these findings using data from a previous human study. In that trial, people taking NSAIDs were less likely to have their depressive symptoms relieved by SSRIs than those not taking NSAIDs.

In fact, 54 percent those not taking these anti-inflammatory painkillers said SSRIs relieved their depressive symptoms, compared with 40 percent of those taking both NSAIDs and SSRIs, Warner-Schmidt said.

In addition to their implications for treating depression, these findings may also be important to Alzheimer's patients, according to lead researcher Nobel Laureate Paul Greengard, the Vincent Astor Professor of the Laboratory of Molecular and Cellular Neuroscience at The Rockefeller University.

"Many elderly individuals suffering from Alzheimer's disease also have arthritic or related diseases and as a consequence are taking both antidepressant and anti-inflammatory medications. Our results suggest that physicians should carefully balance the advantages and disadvantages of continuing anti-inflammatory therapy in patients being treated with antidepressant medications," he said in university news release.

"This is an important observation that needs to be followed up," said Dr. Charles Nemeroff, the Leonard M. Miller Professor and chairman of the psychiatry and behavioral sciences department at the University of Miami Miller School of Medicine.

"If it is possible that drugs that treat pain in any way antagonize the effects of antidepressants, it's really important to know because of the widespread use of both agents," Nemeroff added, noting that depressed patients with chronic pain are difficult to treat.

"The belief has always been that they are difficult to treat because chronic pain wears people down and drives them into depression, but this is a different wrinkle. This would suggest it may be that medications being used to treat their chronic pain may, in fact, be obviating the effects of antidepressants," he said.

While it is too early to draw definitive clinical conclusions from this study, Nemeroff thinks doctors should ask their patients if they are taking NSAIDs when prescribing SSRIs.
"If you treat [patients] with an SSRI and they don't respond, maybe we ought to ask them if they are taking high doses of NSAIDs," Nemeroff said. "If they are, we might think about finding another way to treat their pain or inflammation," he said.